Human blood platelets have been shown to contain high levels of selenium and glutathione peroxidase. The function of the element and enzyme in platelets has not been identified. Platelets also possess a very active lipoxygenase which converts the essential fatty acid arachidonic acid to a hydroperoxy fatty acid (12-HPETE). We have recently obtained preliminary evidence that a selenium glutathione peroxidase is involved in the reduction of the hydroperoxide 12-HPETE to a hydroxy-fatty acid (12-HETE) in the platelet. Furthermore, when the arachidonate platelet lipoxygenase product 12-HPETE is not reduced, we have evidence that it breaks down via a free radical mechanism to trihydroxy and hydroxy-epoxy derivatives of arachidonic acid. The object of this proposal is to investigate the consequences of selenium deficiency in the rat on platelet glutathione peroxidase activity, lipoxygenase metabolism of arachidonic acid and physiological function. Weanling rats will be maintained for periods up to 6 weeks on selenium deficient and supplemented diets. Glutathione peroxidase activity of platelet preparations will be monitored spectrophotometrically and lipoxygenase metabolism will be measured by both radioisotopic thin-layer chromatographic techniques and gas chromatography/mass spectrometry. In related experiments, glutathione peroxidase will be purified from selenium-75 radio-labelled platelets in order to positively confirm the role of selenium in the platelet glutathione peroxidase enzyme. Two physiologically oriented indices of function will also be monitored during selenium deficiency, namely arachidonic acid induced platelet aggregation and the ability of platelets to induce red cell hemolysis via platelet release of hydroperoxyarachidonic acid or its breakdown products. These experiments and those cited above hopefully will provide much needed information on the biochemical and physiological functions on an important, but incompletely understood, trace nutrient.